Very compelling data are available to suggest oxidative stress is an underlying component of many significant human diseases such as diabetes, heart disease, cerebrovascular disease (eg, stroke), peripheral vascular disease, neurodegeneration (Alzheimer's, Parkinson's, ALS and Huntington's disease) as well as aging. However, results to date with antioxidant treatments to mitigate human diseases with oxygen stress as an underlying component of the pathology have been disappointing. Tosk, Inc. has successfully designed an agent to irreversibly bind a traditional antioxidant to an enzyme located in the region where reactive oxygen species are formed. This was done to make the traditional antioxidant more effective. Now Tosk requests Phase I SBIR funding to further explore this approach to produce even more active antioxidants. A total of 15 novel antioxidants will be synthesized and tested in the same animal model used originally to discover the activity of the new antioxidant designed at Tosk. Three of the synthesized molecules will also be tested in one additional animal model of human disease associated with excess oxidative stress as a significant part of the condition's underlying pathology. PUBLIC HEALTH RELEVANCE: Results to date with antioxidant treatments to mitigate human diseases having oxygen stress as an underlying component of the pathology have been disappointing. Tosk, Inc. has successfully designed an agent to irreversibly bind a traditional antioxidant to an enzyme located in the region where reactive oxygen species are formed. This was done to make the traditional antioxidant more effective. Now Tosk requests Phase I SBIR funding to further explore this approach to produce more active antioxidants as well as to evaluate the approach in one additional animal model of human disease associated with excess oxidative stress as a significant part of the conditions underlying the pathology.